2-Deoxy-L-ribose inhibits the invasion of thymidine phosphorylase-overexpressing tumors by suppressing matrix metalloproteinase-9

✍ Scribed by Yuichi Nakajima; Misako Haraguchi; Tatsuhiko Furukawa; Masatatsu Yamamoto; Hayao Nakanishi; Masae Tatematsu; Shin-ichi Akiyama

• Book ID: 102862434
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: French
• Weight: 762 KB
• Volume: 119
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22014

✦ Synopsis

Abstract

Thymidine phosphorylase (TP), an enzyme involved in pyrimidine metabolism, is identical with an angiogenic factor, platelet‐derived endothelial cell growth factor. 2‐Deoxy‐D‐ribose (D‐dRib), the degradation product of thymidine generated by TP activity, has been suggested to be a downstream mediator of TP function. 2‐Deoxy‐L‐ribose (L‐dRib), a stereoisomer of D‐dRib, inhibited the promotion of angiogenesis, tumor growth and metastasis by TP. In our study, we have shown that nude mice inoculated with TP‐overexpressing KB/TP cells had shorter survival times than those injected with control KB/CV cells. KB/TP tumors were also more highly invasive than KB/CV tumors in mice. The expression levels of matrix metalloproteinase (MMP)‐9 in KB/TP tumors were significantly higher than those in KB/CV tumors. L‐dRib and a TP inhibitior, TPI, extended the survival period of KB/TP tumor‐bearing mice. L‐dRib also reduced MMP‐9 mRNA levels in KB/TP tumors. Furthermore, L‐dRib suppressed the mRNA level of MMP‐9 in cultured KB/TP cells, and the invasive activity of the cells. L‐dRib may be useful for the suppression of invasion of TP‐expressing tumor cells. © 2006 Wiley‐Liss, Inc.